Can Laparoscopic Surgery Reduce Fatigue in Women with Endometriosis?-A Pilot Study.

Background: Fatigue is mentioned as one of the most significant symptoms of endometriosis. The impact of laparoscopic endometriosis surgeries on fatigue remains unknown. The aim of this study was to investigate, for the first time, the effect of laparoscopic surgery in endometriosis patients, with the complete removal of endometriotic lesions, on the severity of fatigue. Methods: This is a single-center prospective pilot study including 58 participants. Participants were recruited at the Tertiary Endometriosis Referral Center of the Medical University of Vienna between February 2020 and November 2021. Thirty patients with histologically proven endometriosis were compared to a control group of 28 patients who underwent a laparoscopy for benign gynecologic conditions other than endometriosis. All participants were interviewed using the Fatigue Severity Scale before their surgery and 6 months afterward. Relationships between variables were established using regression analysis and associations were quantified as odds ratios. Results: Fatigue was significantly more severe preoperatively in patients with endometriosis when compared to controls ((odds ratio (OR): 1.82; 95% confidence interval (CI): 1.24-2.67, p < 0.01). Six months postoperatively, the fatigue severity score of endometriosis patients decreased significantly (p < 0.01). In multivariate analysis, fatigue was significantly associated with endometriosis (OR: 4.50, CI: 1.14-17.8, p < 0.05), when adjusted for abdominal pain and menstrual bleeding. Fatigue in patients with endometriosis was not associated with disease stage or the presence of deep endometriosis. Conclusions: Fatigue is a frequent and bothersome symptom in patients with endometriosis. Within our study, we demonstrated for the first time that fatigue responds to surgical treatment. The management of fatigue is crucial to improving patients' quality of life.

Factors Affecting Mode of Birth in Women With Preexisting Diabetes and Gestational Diabetes: A Retrospective Cohort at a Tertiary Referral Center.

Women with preexisting diabetes and gestational diabetes mellitus (GDM) are at higher risk for adverse maternal and neonatal outcomes. However, there is no consensus on a uniform approach regarding mode of birth (MOB) for all forms of diabetes. The aim of the study is to compare MOB in women with preexisting diabetes and GDM and possible factors influencing it. A retrospective cohort study of women with GDM and preexisting diabetes between 2015 and 2021 at a tertiary referral center was conducted. One thousand three hundred eighty-five singleton pregnancies were included. One thousand twenty-two (74.4%) women had a vaginal birth (VB) and 351 (25.6%) a caesarean section. Preexisting diabetes was significantly associated with caesarean section compared to GDM (OR 2.43). Five hundred fifty-one (40.1%) women underwent induction of labor, and 122 (22.1%) women had a secondary caesarean after IOL. Women induced due to spontaneous rupture of membrane (SROM) achieved the highest rate of VB at 93%. The lowest rates of VB occurred if indication for induction was for preeclampsia or hypertension. IOL was significantly less successful in preexisting diabetes with a VB achieved in 56.4% for type 1 diabetes and 52.6% of type 2 diabetes compared to GDM (78.2% in GDM; 81.2% in IGDM; OR 3.25, 95% CI 1.70-6.19, p < 0.001). The rate of VB was higher who were induced preterm compared to women with term IOL (n = 240 (81.9%) vs. n = 199 (73.2%); p < 0.05). Parity, previous VB and SROM favored VB after IOL, whereas preexisting diabetes, hypertension, and IOL after 40 + 0 weeks are independent risk factors for caesarean delivery.

Clinical Factors for Predicting Pharmacotherapy in Twin Pregnancies Complicated by Gestational Diabetes Mellitus.

Controlling blood glucose levels is the main target in pregnant women with gestational diabetes mellitus (GDM). Twin pregnancies are offered the same screening selection and have the same diagnostic criteria as well as treatment of gestational diabetes as singleton pregnancies, even though the risks for pregnancy complications are increased. The aim of this study was to assess the association between predicting factors, OGTT glucose levels and pharmacotherapy requirements in twin pregnancies with GDM. This retrospective cohort study included 446 GDM patients with twin pregnancies (246 managed with lifestyle modifications and 200 requiring pharmacotherapy) over a time period of 18 years. An evaluation of maternal characteristics and a standardized 75 g oral glucose test (OGGT) for glucose concentrations at fasting, 1 h and 2 h were conduced. OGTT glucose levels at fasting (=0 min, p < 0.01) and 1 h (p < 0.01) were significantly associated with the later requirement of pharmacotherapy. Also, clinical risk factors (pre-pregnancy BMI p < 0.01, multiparity p < 0.05, GDM in previous pregnancy p < 0.01, assisted reproduction p < 0.05) showed a predictive accuracy for insulin therapy in twin pregnancies complicated by GDM, whereas age and chorionicity had no effect. OGTT glucose measures in addition to clinical risk factors are promising variables for risk stratification in mothers with GDM and twin pregnancy.

Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome-A Retrospective Analysis.

The 22q11.2 deletion syndrome (22q11.2 DS) is known as the most common microdeletion syndrome. Due to its variable clinical phenotype, prenatal diagnosis can be challenging. The aim of this retrospective study was to evaluate the clinical course and pregnancy outcome of cases with prenatally diagnosed 22q11.2 deletion syndrome (DS) as well as to evaluate the role of prenatal magnetic resonance imaging (MRI) and postmortem examination. In total, 21 cases who underwent prenatal ultrasound examination and pregnancy care at the Department of Obstetrics and Gynecology at the Medical University of Vienna between 2012 and 2022 were included. The majority of the cases were genetically diagnosed using fluorescent in situ hybridization (FISH). The median gestational age (GA) at genetic diagnosis was 23.0 weeks (IQR 21.4-24.8 weeks). CHDs were detected in all fetuses and the most common extracardiac manifestation was thymus hypo/aplasia followed by genitourinary anomalies. Prenatal magnetic resonance imaging (MRI) revealed additional diagnostic information in three of ten cases. Overall, 14 patients opted for drug-induced TOP, of which 9 cases had a feticide prior to the induction of labor. The majority of craniofacial malformations were only detected by autopsy. In conclusion, the majority of cases prenatally diagnosed with 22q11.2 DS had an absent or hypoplastic thymus noted antenatally in addition to the detected CHD, and almost half of the cases had another extracardiac malformation of predominantly genitourinary origin. Furthermore, prenatal MRIs confirmed previously detected malformations, but only provided additional diagnostic information in three out of ten cases, whereas postmortem examination diagnosed most of the craniofacial anomalies and should always be conducted, serving as an important quality indicator for prenatal imaging.

Factors Influencing the Duration of Termination of Pregnancy for Fetal Anomaly with Mifepristone in Combination with Misoprostol.

This study's aim was to determine relevant factors that influence the time interval between first induction and fetal expulsion in late termination of pregnancy (TOP) and TOP after previous feticide for severe fetal malformation with a mifepristone-misoprostol regime. This retrospective study included 913 TOPs from a single tertiary care referral center. In 197 out of 913 TOPs, a previous feticide had been performed due to advanced gestational age (after 22 + 0 weeks of gestation). Induction was accomplished using 600 mg mifepristone followed by 400 µg misoprostol. The interval between first induction with misoprostol and fetal expulsion was examined. Univariate and multivariate logistic regression analysis were used to predict an induction interval of 12 h or less. The median gestational age at induction of labor was 18.9 weeks of pregnancy. In 487 (53.3%) cases women delivered within 12 h; in 344 (37.7%) cases the induction interval was between 12 h and 36 h. In 82 (9%) cases induction took longer than 36 h. Factors that were significantly associated with a delivery duration of <12 h were a lower gestational age at induction (OR 0.87; 95% CI 0.84-0.89; p < 0.001) and a history of at least one previous vaginal delivery (OR 1.57; 95% CI 1.20-2.05; p < 0.001). Factors that had no impact included previous cesarean section, performing feticide before induction and maternal age. Maternal BMI showed a non-significant trend.

Use of polysaccharide hemostatic agent (HaemoCer™) in breast cancer surgery to reduce postoperative complications: A randomised controlled trial.

Postoperative wound-site bleeding, tissue inflammation and seroma formation are well-known complications in the field of breast surgery. Hemostatic agents consisting of polysaccharides may be used intra-operatively to minimise postoperative complications. We conducted a prospective randomised-controlled, single-centre study including 136 patients undergoing breast-conserving surgery for invasive or intraductal breast cancer. Of these, 68 patients were randomised to receive an absorbable polysaccharide hemostatic agent into the wound site during surgery, while 68 patients were randomised to the control group and did not receive any hemostatic agent. Primary outcome was the total volume of postoperative drained fluid from the surgical site. Secondary outcomes were the number of days until drain removal and rate of immediate postoperative surgical site infection Patients in the intervention group had significantly higher drainage output volumes compared with the control group 85 mL (IQR 46.25-110) versus 50 mL (IQR 30-75), respectively; (P = .003). Univariable linear regression analyses showed a significant association between the surgical specimen and the primary outcome (P < .001). After multivariable analysis, the use of absorbable polysaccharide hemostatic product was no longer significantly associated with a higher drainage output and only the size of the surgical specimen remained a significant predictor. The number of days until drainage removal and the postoperative seroma formation were higher in the intervention group (P = .004) and (P = .003), respectively. In our study, intraoperative application of polysaccharide hemostatic agent during breast-conserving surgery did not decrease postoperative fluid production. Only the size of the surgical specimen was significantly associated with postoperative drainage volume.

Corrected Allele Frequency of BRCA1/2 Mutations Is an Independent Prognostic Factor for Treatment Response to PARP-Inhibitors in Ovarian Cancer Patients.

PARP inhibitors (PARPi) have increased treatment options in ovarian cancer, particularly in patients with BRCA1/2 mutations, although there are still marked differences in the duration of patients' response to this targeted therapy. BRCA testing is routinely performed in tumor tissue of ovarian cancer patients. The resulting molecular pathological findings include the genetic nomenclature of the mutation, the frequency of the mutated allele (variant allele frequency, VAF), and the tumor cell content. VAF measures the percentage of mutated alleles from the total alleles in the cells of the examined tissue. The aim of this study was to investigate the significance of VAF on the therapeutic response to PARPis in ovarian cancer patients. Epithelial ovarian cancer patients harboring BRCA1/2 tumor mutations, who underwent germline testing and received PARPi therapy at the Medical University of Vienna (n = 41) were included in the study. Corrected VAF (cVAF) was calculated based on VAF, tumor cell content, and germline mutation. Patients were divided into two groups based on their cVAF. Median PFS under PARPi in patients with low cVAF was 13.0 months (IQR [10.3-not reached]) and was not reached in the high cVAF group. High cVAF was significantly associated with longer PFS in the multivariate analysis (HR = 0.07; 95% CI [0.01-0.63]; p = 0.017). In conclusion, high cVAF was associated with a significantly better response to PARPi in this study population.

Gestational Diabetes Mellitus in Pregnant Women with Beta-Thalassemia Minor: A Matched Case-Control Study.

Pregnancy in women with thalassemia minor is considered safe. However, a higher incidence of maternal and neonatal complications in women with the disorder has been reported in the literature. This study aimed to determine whether there is an increased risk of gestational diabetes mellitus (GDM) in pregnant women with beta-thalassemia minor. We conducted a retrospective matched case-control study of 230 pregnant women who delivered at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna between the years 2008 and 2020, whereof 115 women had beta-thalassemia minor. We found no significant difference in the occurrence of GDM between the case group and control group of age and BMI-matched healthy women. However, we observed a significantly lower hemoglobin (Hb) and hematocrit (Ht) level during the first, the second, and the third trimesters of pregnancy, and postpartum (all: p < 0.001) among women with beta-thalassemia minor compared to the healthy controls. Neonates of women with beta-thalassemia were more likely to experience post-natal jaundice and excessive weight loss (p < 0.001). We conclude that GDM is not more likely to occur in pregnant women with beta-thalassemia minor. However, clinicians should be made aware of the risk of adverse maternal and neonatal outcomes. Furthermore, women with beta-thalassemia minor should undergo regular laboratory screening and multidisciplinary pregnancy care.

Clinical Course and Outcome of Non-Immune Fetal Hydrops in Singleton Pregnancies.

Nonimmune fetal hydrops is a condition defined by abnormal fluid accumulation in two or more body compartments. The aim is to evaluate factors associated with adverse outcome in diagnosed fetal hydrops and to investigate the aspects for the decision making in the case of termination of pregnancy. Therefore, a retrospective data analysis of pregnancies complicated by non-immune hydrops fetalis between 2004 and 2018 was performed in a single tertiary referral center. Of 361 pregnancies with diagnosed fetal hydrops, in 183 cases (50.7%), the parents decided to terminate the pregnancy. A strong relationship between etiology and termination of pregnancy was demonstrated, whereas the highest rates of termination of pregnancy were found if a chromosomal aberration was diagnosed. Of the remaining 178 cases, 51 cases (28.7%) had a miscarriage, 33 cases (18.5%) had an intrauterine fetal death, and 94 cases (52.8%) were live born, whereas 26 (27.7%) of these offspring died within the first week of life. The risk of an adverse outcome increased with lower gestational age at diagnosis (p < 0.001). A nuchal translucency thickness greater than 2.5 mm was associated with an adverse outcome (p < 0.01). Furthermore, pregnancies with adverse outcome had significantly more affected compartments (median: 3; IQR 2), compared with live born cases (median: 2; IQR 1; p < 0.01). In conclusion, adverse outcome in pregnancies with fetal hydrops was associated with a lower gestational age at diagnosis, nuchal translucency greater than 2.5 mm and a higher count of affected compartments. These results confirm that a precise clinical workup to identify the underlying etiology of non-immune fetal hydrops is essential for a better prognostic assessment and accurate counselling of parents.

Singleton exome sequencing of 90 fetuses with ultrasound anomalies revealing novel disease-causing variants and genotype-phenotype correlations.

Exome sequencing has been increasingly implemented in prenatal genetic testing for fetuses with morphological abnormalities but normal rapid aneuploidy detection and microarray analysis. We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing (sES; 75 fetuses) or to a lesser extent (15 fetuses) a multigene panel analysis of 6713 genes as a primary tool for the detection of monogenic diseases. The detection rate of pathogenic or likely pathogenic variants in this study was 34.4%. The highest diagnostic rate of 56% was in fetuses with multiple anomalies, followed by cases with skeletal or renal abnormalities (diagnostic rate of 50%, respectively). We report 20 novel disease-causing variants in different known disease-associated genes and new genotype-phenotype associations for the genes KMT2D, MN1, CDK10, and EXOC3L2. Based on our data, we postulate that sES of fetal index cases with a concurrent sampling of parental probes for targeted testing of the origin of detected fetal variants could be a suitable tool to obtain reliable and rapid prenatal results, particularly in situations where a trio analysis is not possible.

Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study.

Prenatal exposure to perfluoroalkyl substances (PFAS), bisphenol A (BPA), lead (Pb), total mercury (THg), and methylmercury (MeHg) can affect fetal development. Factors influencing placental transfer rate of these toxins are poorly investigated. Whether prenatal exposure to pollutants has an effect on birth weight is incompletely understood. We therefore aimed (1) to determine placental transfer rates of PFAS, BPA, Pb, THg, and MeHg, (2) to analyze relationships between fetal exposure and birth outcome and (3) to analyze gene variants as mediators of placental transfer rates and birth outcome. Two hundred healthy pregnant women and their newborns participated in the study. BPA, 16 PFAS, THg, MeHg, and Pb were determined using HPLCMS/MS (BPA, PFAS), HPLC-CV-ICPMS (MeHg), CV-AFS (THg), and GF-AAS (Pb). Questionnaires and medical records were used to survey exposure sources and birth outcome. 20 single nucleotide polymorphisms and two deletion polymorphisms were determined by real-time PCR from both maternal and newborn blood. Genotype-phenotype associations were analyzed by categorical regression and logistic regression analysis. Specific gene variants were associated with altered placental transfer of PFAS (ALAD Lys59Asn, ABCG2 Gln141Lys), THg (UGT Tyr85Asp, GSTT1del, ABCC1 rs246221) and Pb (GSTP1 Ala114Val). A certain combination of three gene polymorphisms (ABCC1 rs246221, GCLM rs41303970, HFE His63Asp) was over-represented in newborns small for gestational age. 36% of Austrian and 75% of Slovakian mothers had levels exceeding the HBM guidance value I (2 µg/L) of the German HBM Commission for PFOA. 13% of newborns and 39% of women had Ery-Pb levels above 24 µg/kg, an approximation for the BMDL01 of 12 µg/L set by the European Food Safety Authority (EFSA). Our findings point to the need to minimize perinatal exposures to protect fetal health, especially those genetically predisposed to increased transplacental exposure.

Simpson-Golabi-Behmel-Syndrome in Dichorionic-Diamniotic Twin Pregnancy.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare x-linked overgrowth syndrome with distinct clinical features, which is difficult to diagnose prenatally. We report the diagnosis of SGBS in dichorionic-diamniotic twin pregnancies in the first trimester by ultrasound and genetic testing. The affected fetus developed polyhydramnios and the cervical length of the mother decreased significantly. To save the unaffected twin, a selective feticide of the affected fetus was performed. Finally, the patient underwent preterm caesarean section due to premature rupture of membranes in the dead twin, and also intrauterine infection. While SGBS has been reported, this was the first case in a multiple pregnancy, with possible consequences for the healthy twin. In conclusion, SGBS is a rare condition, which should be considered in the differential diagnosis of prenatal overgrowth syndromes and associated malformation.

Genetic diagnosis and clinical evaluation of severe fetal akinesia syndrome.

OBJECTIVE: In this retrospective study, we describe the clinical course, ultrasound findings and genetic investigations of fetuses affected by fetal akinesia. MATERIALS AND METHODS: We enrolled 22 eukaryotic fetuses of 18 families, diagnosed with fetal akinesia between 2008 and 2016 at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna. Routine genetic evaluation included karyotyping and chromosomal microarray analysis. Retrospectively, exome sequencing was performed in the index case of 11 families, if stored DNA was available. Confirmation analyses and genetic diagnosis of siblings were performed by using Sanger sequencing. RESULTS: Whole exome sequencing identified pathogenic variants of CNTN1, RYR1, NEB, GLDN, HRAS and TNNT3 in six cases of 11 families. In three of these families, the variants were confirmed in the respective sibling. CONCLUSIONS: The present study demonstrates a high diagnostic yield of exome sequencing in fetuses affected by akinesia syndrome, especially if family history is positive. Still, in a large part the underlying genetic cause remained unknown, whereas precise clinical evaluation in combination with exome sequencing shows to be the best tool to find the disease causing variants.

Genetic association in female stress urinary incontinence based on proteomic findings: a case-control study.

INTRODUCTION AND HYPOTHESIS: Previous studies have indicated a hereditary component of stress urinary incontinence; however, evidence on candidate genes or single-nucleotide polymorphisms (SNPs) is scarce. We hypothesize a genetic association of female stress urinary incontinence based on significant differences of the urinary and serum proteomic pattern in the identical study population. METHODS: Case-control study of 19 patients and 19 controls. We searched for known SNPs of SUI candidate genes (COL1A1, MMP1, SERPINA5, UMOD) in the database of short genetic variations and PubMed. Genomic DNA was isolated using QIAamp DNA Blood Midi Kit (Qiagen). We performed Sanger sequencing of selected exons and introns. RESULTS: The rs885786 SNP of the SERPINA5 gene was identified in 15 cases and 10 controls (p = 0.09). The rs6113 SNP of the SERPINA5 gene was present in 4 controls compared to 0 cases (p = 0.105). The rs4293393, rs13333226 and rs13335818 SNPs of the UMOD gene were identified in five cases and two controls (p = 0.20), the rs1800012 SNP of the COL1A1 gene in five cases versus four controls (p = 0.24) and the homozygous rs1799750 SNP of the MMP1 gene in eight cases versus five controls (p = 0.18). The combination of the rs885786 SNP of the SERPINA5 gene and rs179970 SNP of the MMP1 gene was detected in ten cases versus five controls (p = 0.072). CONCLUSIONS: We found nonsignificant trends toward associations of SNPs on the SERPINA5, UMOD and MMP1 gene and SUI.

Prenatal detection of right aortic arch.

PURPOSE: To examine an unselective population of fetuses with right aortic arch (RAA) and suggest perinatal management. Second, to evaluate the importance and possible implication of fetal MRI in those cases. METHODS: Retrospective study of 36 patients with RAA diagnosed prenatally between 2006 and 2017 in a tertiary referral center. RESULTS: 32 fetuses were diagnosed with RAA and 4 with double aortic arch (DAA). 7 (19, 5%) cases had intracardiac abnormalities. Tetralogy of the Fallot was the most frequent one. Other extracardiac malformations were observed in 11/36 (30, 6%). Karyotype was available in 16 (44, 5%) cases. Two had 22q11.2 microdeletion, two trisomy 21, and one 20p12.2 duplication. Two needed surgery for respiratory symptoms. A newborn was identified with epilepsy, Lennox-Gastaud syndrome and Pallister-Killian syndrome postnatally and another one with showed hyperreflexia and premature closer of the fontanelle. Three feticides were performed for pregnancy termination in one case with 22q11 deletion, trisomy 21, and partial agenesis of corpus callosum. CONCLUSION: RAA can be detected by fetal echocardiography and it is associated with other cardiac or non-cardiac abnormalities, 22q11 microdeletion, trisomy 21, and other chromosomal abnormalities. karyotyping should be offered in any case of RAA, irrespective of co-existing malformations. Fetal MRI is a promising diagnostic tool for assessment of congenital cardiovascular abnormalities and extracardiac anomalies.

Is vaginal progesterone treatment associated with the development of gestational diabetes? A retrospective case-control study.

PURPOSE: To determine the incidence of gestational diabetes mellitus (GDM) in pregnant women who received vaginal progesterone due to short cervical length or to prevent recurrent preterm birth. METHODS: In this retrospective study, we included 190 women with singleton pregnancies at risk for preterm birth who received vaginal natural progesterone (200 mg daily between gestational weeks 16 + 0 and 36 + 0) for a minimum of 4 weeks and delivered > 28 weeks. The control group consisted of 242 age- and body mass index (BMI)-matched patients without progesterone administration. Data were acquired from a database containing prospectively collected information. Patients with pre-existing diabetes, and conception after in vitro fertilisation procedure were excluded. RESULTS: The incidence of GDM did not differ significantly between the progesterone-treated and the control group (14.7% vs. 16.9%, respectively; p = 0.597). In a binary regression model, patients with higher pre-pregnancy BMI (OR 1.1; p = 0.006), and those with a family history of diabetes had a higher risk for GDM development (OR 1.8; p = 0.040), whereas vaginal progesterone treatment had no significant influence (p = 0.580). CONCLUSION: The use of vaginal progesterone for the prevention of recurrent preterm delivery and in women with a short cervix does not seem to be associated with an increased risk of GDM.

Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients.

BACKGROUND: Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis. METHODS: Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP) endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used. RESULTS: We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p = 0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%). The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001). CONCLUSION: Our findings support the hypothesis that upregulation of stem cell-related factors contribute to the establishment of endometriotic lesions. TRIAL REGISTRATION: The study was approved by the institutional review board (545/2010 on 6th of May 2014) of the Medical University of Vienna ( http://ethikkommission.meduniwien.ac.at/fileadmin/ethik/media/dokumente/register/alle_2010.pdf ).

Comprehensive study of angiogenic factors in women with endometriosis compared to women without endometriosis.

OBJECTIVE: Endometriosis is a benign gynaecological disease, affecting women during their reproductive years. Angiogenesis represents a crucial step in the pathogenesis of endometriosis, because endometriotic lesions require neovascularization. In this study several angiogenesis-related genes have been studied in the context of endometriosis. Some of the analyzed angiogenic factors as well as their interactions were studied the first time regarding a possible association with endometriosis. STUDY DESIGN: This case-control study consisted of 205 biopsies of 114 patients comprising 61 endometriosis patients and 53 control patients. Among them in 29 cases paired samples were obtained. VEGFA, VEGFR2, HIF1A, HGF, NRP1, PDGFB, FGF18, TNFα, TGFB2, EPHB4, EPO and ANG mRNA expression was analyzed by qRT-PCR in ectopic tissue samples, in eutopic endometrium of women with and without endometriosis, and in unaffected peritoneum of women with and without endometriosis. RESULTS: VEGFR2, HIF1A, HGF, PDGFB, NRP1 and EPHB4 are overexpressed in ectopic lesions compared to eutopic tissues. VEGFR2, HGF, PDGFB, NRP1, and EPHB4 showed highest mRNA levels in peritoneal implants, in contrast HIF1A showed the highest expression in ovarian endometriomas. Correlation analyses of angiogenic factors in ectopic lesions revealed the strongest associations between VEGFR2, PDGFB, and EPHB4. We further showed a significant upregulation of VEGFR2, HIF1A and EPHB4 in eutopic endometrium of women with endometriosis compared to that of controls and a trend towards upregulation of HGF. Additionally, a significant downregulation for HIF1A, HGF and EPHB4 was observed in unaffected peritoneal tissues of women with endometriosis compared to controls. CONCLUSION: We identified new genes (EPHB4 and NRP1) that may contribute to angiogenesis in endometriosis beside known factors (VEGFA, VEGFR2, HIF1A, HGF, and PDGFB). Correlation studies revealed the putative importance of EBHB4 in association with endometriosis. Our analyses support preliminary reports that angiogenic factors seem to be differently expressed in peritoneal implants, ovarian endometriomas and deep infiltrating endometriosis. Our observation that angiogenic factors are differently expressed in the unaffected peritoneum of women with endometriosis compared to women without endometriosis underlines the importance of the peritoneum in the establishment of endometriosis.